Sengupta 

and Dutta  Middle East Fertility

Middle East Fertility Society Journal (2022) 27:14
https://doi.org/10.1186/s43043-022-00104-8 Society Journal

REVIEW Open Access

N‑acetyl cysteine as a potential regulator

of SARS‑CoV‑2‑induced male reproductive
disruptions
Pallav Sengupta1*    and Sulagna Dutta2    

Abstract 
Background:  The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), causing the coronavirus disease
2019 (COVID-19), has shown its persistent pandemic strength. This viral infectivity, kinetics, and the mechanisms of its
actions in human body are still not completely understood. In addition, the infectivity and COVID-19 severity report-
edly differ with patient’s gender with men being more susceptible to the disease. Thus, different studies have also
suggested the adverse impact of COVID-19 on male reproductive functions, mainly emphasizing on high expressions
of angiotensin-converting enzyme 2 (ACE2) in the testes that allows the viral entry into the cells.
Main body:  The N-acetylcysteine (NAC), a potent therapeutic agent of COVID-19, may be effective in reducing the
impairing impacts of this disease on male reproductive functions. NAC acts as mucolytic agent by reducing sulfide
bonds in the cross-linked glycoprotein matrix in mucus owing to its free sulfhydryl group. Since NAC also breaks the
viral disulfide bonds required for the host cell invasion, it may help to prevent direct SARS-CoV-2 invasion into the tes-
ticular cells as well. NAC also acts as a potent anti-inflammatory and antioxidant, directly scavenging reactive oxygen
species (ROS) and regulating the redox state by maintaining the thiol pool being a precursor of cysteine (an essential
substrate for glutathione synthesis). Since it is suggested that male reproductive impairment in COVID-19 patient may
be caused by secondary immune responses owing to systemic inflammation and OS, the anti-inflammatory and anti-
oxidant properties of NAC explained above may attribute in protecting the male reproduction functions from these
COVID-19-mediated damages.
Conclusion:  This article explains the mechanisms how NAC treatment for COVID-19 may prevent the infection-medi-
ated disruptions in male reproduction.
Keywords:  COVID-19, SARS-CoV-2, Male infertility, N-acetyl cysteine

Background it as a pandemic disease on March 11 2020 [1, 2]. The

The coronavirus disease 2019 (COVID-19) is a unique
infectious disease caused by a novel coronavirus,
reported to be originated from the Wuhan city, China, in
December 2019. Following its outstretch over 100 coun-
tries, the World Health Organization (WHO) asserted
*Correspondence: pallav_cu@yahoo.com
1
Department of Physiology, Faculty of Medicine, Bioscience and Nursing,
MAHSA University, Jenjarom, Selangor, Malaysia
Full list of author information is available at the end of the article
disease is caused by the severe acute respiratory syn-
drome coronavirus-2 (SARS-CoV-2), and men are more
susceptible to infection than women [3]. The genomic
study of SARS-CoV-2 has explored about 79% resem-
blance with SARS-CoV which became epidemic in 2002
[4]. Thus, the SARS-CoV-2 may part common host cell
infection contrivances with SARS-CoV. Angiotensin-con-
verting enzyme-2 (ACE2) receptor plays a key role in the
COVID-19 pathogenesis, while transmembrane protease,
serine-2 (TMPRSS2) mediates priming of viral spike pro-
teins with ACE2 [5]. The association of the host ACE2

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Sengupta and Dutta Middle East Fertility Society Journal
and the spike glycoprotein of SARS-CoV-2 causes fusion
of host-pathogen membrane surfaces followed by inter-
nalization of the pathogen [6].
Main body
Mechanism of testicular infection of SARS‑CoV‑2
The testes have been found to have nearly the greatest
levels of ACE2 mRNA and protein expression among the
other bodily tissues (Fig.  1), raising the idea of a poten-
tial hazard to male fertility as a result of SARS-CoV-2
infection in these tissues [5]. Furthermore, testicular cells
show much higher amounts of ACE2 than ovarian cells,
whereas ovarian cells express considerably lower levels of
ACE2 [7–9], which may also support higher vulnerabil-
ity of male gonadal functions including steroidogenesis,
towards SARS-CoV-2-mediated impairment. The activa-
tion of the androgen receptor is required for the tran-
scription of the TMPRSS2 gene. Furthermore, the gene
loci for the androgen receptor and the ACE2 enzyme are
found on chromosome X [10, 11]. Polymorphisms on this
chromosome, as well as endogenous androgen effects,
have been linked to TMPRSS2 gene transcription and
Fig. 1  Expressions of ACE2 in different systems (A), male reproductive organs (B), and testicular cells (C) [source: Human Protein Atlas, 2020]
(2022) 27:14 Page 2 of 6
activation of the antiviral enzyme ACE2, which facilitates
viral penetration in target cells [12].
The Renin-Angiotensin-Aldosterone System (RAS) is
regulated by the angiotensin-converting enzyme (ACE).
Through the ACE2/angiotensin (1-7)/MAS axis, ACE2
counteracts the negative effects of the ACE/RAS path-
way [13]. Renin and ACE activities are required for physi-
ological angiotensin II activation. Renin is synthesized
when the juxtaglomerular apparatus (JG) of the afferent
arterioles of the kidneys is activated. Renin cleaves angi-
otensinogen into angiotensin (Ang) I once it is released
into the bloodstream. Although Ang I is not physiologi-
cally active, it is a precursor to Ang II. ACE catalyzes the
conversion of Ang I to Ang II [14]. Ang II binds to angio-
tensin II type I and type II receptors in various tissues.
Ang II activates a number of signaling pathways in cells,
including serine/threonine kinase, ERK, JNK/MAPK,
and PKC [15] and has been proven in studies to elevate
cytokines (IL-6, TNF-α, and others), oxidative dam-
age caused by ROS, endothelial injury caused by block-
ing NO generation, and vasoconstriction. The binding of
spike(S) glycoprotein to ACE2 causes lesser expression of
 Sengupta and Dutta Middle East Fertility Society Journal
that enzyme; thus, accumulation of Ang II will take place
due to the activation of ACE. This reduced ACE2 is not
able to produce the vasodilator heptapeptide angioten-
sin 1-7 from Ang I, and this causes the initiation of lung
injury. Accumulated Ang II is responsible for the over-
stimulation of its type-I receptor which is associated with
various pathological conditions [16]. Both human ACE2
and the SARS-CoV-2 S-glycoprotein have been targeted
in therapeutic strategies for the exploration of new treat-
ment plans such as antiviral molecules and monoclonal
antibodies as well as isolation of existing drug molecules
which can prevent the interaction between the host and
SARS-CoV-2. As for the two subunits of the S-glycopro-
tein, S1 facilitates the viral bonding with the host cells,
whereas S2 acts as fusion protein for viral membrane
[17].
The process of SARS-CoV-2 evasion depends on
S-glycoprotein cleavage at S1/S2 multibasic cleavage site
(MBCS), mainly with the presence of human furin, and
this cleavage site plays a vital role to facilitate the entry
of virus into the infected cells [18]. Furin, as termed as
paired basic amino acid cleaving enzyme (PACE), has
been found in the fluid from the mid-caput to the distal
corpus regions of the epididymis and also in testis of vari-
ous domestic mammals through immunochemistry and
mass spectrometry analyses [19]. This indicated the pos-
sibility of this virus-mediated impairments in sperm pro-
duction or maturation. So, the expression of FUR gene
or inhibition of furin or obstructions and/or spoiling to
form MBCS for the interaction between S1/S2 complex
and furin are now the new strategies of target for the
therapeutic approaches.
N‑acetylcysteine, SARS‑CoV‑2, and male reproduction
N-acetylcysteine (NAC) has been proposed as a poten-
tial treatment, preventive and/or adjuvant against SARS-
CoV-2 as it is having two major activities: first, due to
presence of its free sulfhydryl group, NAC reduces the
sulfide bonds in the cross-linked glycoprotein matrix
in mucus thus reduced mucus viscosity and showing
a mucolytic property [20, 21]. Second, being a potent
antioxidant, NAC may exert direct effects on some reac-
tive oxygen species (ROS), whereas it is a precursor of
cysteine (an essential substrate for glutathione synthe-
sis) and also regulates the redox state by maintaining
the thiol pool [20]. Considering these properties, it can
be hypothesized that NAC could negatively affect SARS-
CoV-2 activity for the following mechanisms (Fig. 2).
NAC and blocking of the SARS‑Cov‑2 evasion route
The envelop protein or E-protein of SARS-CoV (geneti-
cally correlating to SARS-CoV-2) is ranging from 8.4
to 12 kDa in its size with the presence of 76–109 amino
(2022) 27:14 Page 3 of 6
acids. Its primary structure is short hydrophilic amine
terminus group of 7–12 amino acids, and secondary
structure consists of short hydrophobic 25 amino acid
transmembrane domain with carboxyl group terminus
[22]. The E-protein of SARS-CoV-2 possesses a motif of
triple cysteine (NH2-...L-Cys-A-Y-Cys-Cys-N...-COOH)
followed by the transmembrane domain which links with
another identical motif of S protein (NH2-... S-Cys-G-
S-Cys-Cys-K...-COOH) [22]. Disulfide bond was recog-
nized to be responsible for the interaction of both the
motifs [22], and NAC may break those disulfide bonds
and thus may prevent the possibility of host cell inva-
sion. Thus, it may be suggested that despite the high
ACE2 expressions in the testicular cells, treatment with
NAC may help to prevent direct SARS-CoV-2 invasion
into these cells as well. In case of sperms, studies have
shown that NAC helps to maintain sperm DNA integrity
by improved replacement of histones with protamine [23,
24]. Aberrant sperm protamine deposition or chromatin
condensation can increase possibilities of sperm DNA
damage [25], and impaired spermiogenesis (histone to
protamine exchange) seems to be a major factor in male
fertility [26].
Through an in  vitro study, it has been observed that,
in dose-dependent manner, NAC may reduce the bind-
ing of angiotensin II with its type 1 receptor [27]. NAC
may block imprudent synthesis of angiotensin II which
cannot be converted to angiotensin 1-7 by the activation
of ACE2, thus lowering the possibility and/or severity of
the infection. In one study, isosorbide dinitrate (a vaso-
dilator) was applied to six patients for 48 h, but at 24 h,
2 g of NAC was applied followed by another dose of 5 mg/
kg/h. For the first 24 h of isosorbide dinitrate application,
plasma concentration of angiotensin II was increased,
but NAC was applied later on; it causes the sudden fall
of angiotensin II plasma concentrations from 28 ± 4 to
14 ± 2 ng/l (p < 0.05) [28]. This observation suggests that
NAC may allow protection from the pathological effects
of angiotensin II by inhibiting the ACE, which can be
considered as a possible utilitarian venture in view of
SARS-CoV-2 infection.
NAC: as a potential antioxidant
Being a potent antioxidant biomolecule, NAC may com-
bat against the production of ROS and most importantly
the cytokine storm creating the emergence of oxidative
stress (OS) [29, 30]. It is supposed that the immunopa-
thology of SARS-CoV and SARS-CoV-2 is similar and
triggers an immunological response incorporating vari-
ous types of pro-inflammatory cytokines like IL-1, IL-2,
IL-4, TNF, and IFNs. Categorization of the IFNs follows
type-I (IFN-α and β), type-II (IFN-γ), and type-III. SARS-
CoV infection have been shown to suppress the type-I
Sengupta and Dutta Middle East Fertility Society Journal (2022) 27:14 Page 4 of 6

Fig. 2  Possible mechanisms of NAC-mediated protections against male reproductive disruptions caused by SARS-CoV-2 infection. A Due to
presence of its free sulfhydryl group, NAC reduces the sulfide bonds in the cross-linked glycoprotein matrix in mucus thus reduced mucus
viscosity and showing a mucolytic property. B NAC may reduce the binding of angiotensin II with its type 1 receptor. NAC may block imprudent
synthesis of angiotensin II which cannot be converted to angiotensin 1-7 by the activation of ACE2 thus lowering the possibility and/or severity
of the infection. C NAC may lead to amplification of signal cascades triggered by toll-like receptor 7 and mitochondrial antiviral signal protein in
restoration of SARS-CoV-2-mediated type-I interferon (IFN) production and inhibition of NFkβ (nuclear factor kappa B) mediated upregulation
of pro-inflammatory genes. D Being a potent antioxidant, NAC may exert direct effects on some reactive oxygen species (ROS), whereas it is a
precursor of cysteine (an essential substrate for glutathione synthesis) and also regulates the redox state by maintaining the thiol pool

IFNs by impairing signal transducer and activator of tran-
scription 1 (STAT1), antagonizing IFN. During SARS-
CoV-2 infection, the above process leads to delayed IFN
response by cytokine storm syndrome. NAC may lead
to amplification of signal cascades triggered by toll-like
receptor 7 and mitochondrial antiviral signal protein in
restoration of SARS-CoV-2-mediated type-I IFN produc-
tion [29]. NF-κB has been reported to cause the cytokine
storm by accelerating the synthesis of several pro-inflam-
matory cytokines and acts as a mediator of SARS-CoV-2
pathology. This mechanism includes macrophage and
neutrophil infiltrations resulting irretrievable degenera-
tion of infected epithelium. On the other hand, an in vitro
model of influenza A and influenza B has shown that
administration of NAC reduced the activation of NF-κB
[31] probably by restoring the thiol pools and followed by
the ROS scavenging mechanism. Similarly, recent clinical
study has explained that the progress of pathologic con-
ditions may be linked with sudden fall of GSH levels
and reflecting the elevated production of ROS. There-
fore, cases with severe symptoms of COVID-19 infec-
tion would have been evident with increased ROS level
and decreased GSH level hence the higher value of cal-
culating ROS/GSH ratio than the cases with mild or less
severe symptoms of infection [32]. Since it is suggested
that male reproductive impairment in COVID-19 patient
may be caused by secondary immune responses owing to
systemic inflammation and OS [10], the anti-inflamma-
tory and antioxidant properties of NAC explained above
may attribute in protecting the male reproduction func-
tions from these COVID-19-mediated damages.
Administration of 100 mg/kg continuous intravenous
infusion of NAC (daily for 3 days) was also reflected a
positive clinical response in a woman suffering from
 Sengupta and Dutta Middle East Fertility Society Journal
pneumonia, infected with influenza virus (H1N1),
although oseltamivir was also applied to the patient
during her treatment [33]. Besides that, administra-
tion of 600 mg of NAC (twice daily) was shown to be
effective to reduce the symptoms related to influenza
among the older patients (≥ 65  years) [34]. On the
contrary, some studies denied the any beneficial effect
of NAC administration through in  vitro or in  vivo
model of experiments [35].
Without considering the clinical proof for the
COVID-19 diagnosis, many medicines had been placed
regarding the pandemic enormous health hazard; NAC
is within them [36]. Administration of NAC by any of
three routes (e.g., orally, intravenous, or inhaled) as an
adjacent diagnosis in patients with mild symptoms of
COVID-19 has been placed as less expensive clinical
treatment. Recently, there are few clinical try-outs con-
sidering the probable usage of NAC for the treatment
of COVID-19, as an example, efficiency and safety of
nebulized heparin (NAC) in COVID-19 patients by
the examination of pulmonary function improvement
(HOPE) “clinical try-out is objected at governing the
efficiency of nebulized NAC and Heparin in the ven-
tilated COVID-19 patients” [37]. The objective is to
create more ventilator-free days among the patients
who are hospitalized with mild to severe COVID-19
symptoms. One more current study has been reported
that the patients intaking NAC intravascularly 6 g/
day along with other clinical diagnosis designated for
COVID-19 [21, 38]. Administration of NAC orally
(600 mg/day) can play a preventive measure, mainly
on those carriers who are continuously been exposed
to probable SARS-CoV-2 (health workers). The afore-
mentioned application can be proven to be an impor-
tant approach as several health care workers in the
USA, Italy, China, Mexico, etc., had become contami-
nated while caring the hospitalized patients in spite of
the use of personal protective equipment (PPE). This
administration of NAC has been proved as beneficial
not only for health care professionals but also for oth-
ers those who are unable to keep them self-isolated. If
the effectiveness of NAC administration is proved in a
long run, then it can form a plateau in the exponential
contagion curve among many countries, only after sev-
eral clinical trials. The confirmation of probable use of
NAC as an element in preventing the disease caused by
SARS-CoV-2 needs basic laboratory and clinical stud-
ies. The previously mentioned will need to be one of
the countless efforts to find out the auxiliary treatment
which can be either novel or not objected at pointing
the recent COVID-19 outbreak along with minimizing
the contamination process from one person to other.
(2022) 27:14 Page 5 of 6
Conclusion
NAC is a potent agent in the treatment of COVID-19.
Because of its free sulfhydryl group, NAC functions as a
mucolytic agent by decreasing sulfide bonds in the cross-
linked glycoprotein matrix of mucus. NAC may also
inhibit direct SARS-CoV-2 invasion into testicular cells
by breaking the viral disulfide bonds essential for host
cell invasion. Since secondary immune responses result-
ing from systemic inflammation and OS are suggested
to cause male reproductive impairment in COVID-19
patients, the anti-inflammatory and antioxidant proper-
ties of NAC may contribute to protecting male reproduc-
tion functions from COVID-19-induced damage. The
article provides an idea regarding the possible processes
by which NAC treatment for COVID-19 may prevent
infection-mediated abnormalities in male reproduction,
and thus, it encourages in-depth studies in this field so
that the clinical potencies of NAC as male reproductive
ameliorator in SARS-CoV-2 infections are completely
revealed.
Acknowledgements
Not applicable.
Authors’ contributions
PS and SD designed and planned the article, wrote the article, and made the
final revisions. Both the authors have read and approved the manuscript.
Funding
None.
Availability of data and materials
Not applicable.
Declarations
Ethics approval and consent to participate
Not applicable.
Consent for publication
Not applicable.
Competing interests
The authors declare that they have no competing interests.
Author details
1
 Department of Physiology, Faculty of Medicine, Bioscience and Nursing,
MAHSA University, Jenjarom, Selangor, Malaysia. 2 Department of Oral Biology
and Biomedical Sciences, Faculty of Dentistry, MAHSA University, Jenjarom,
Selangor, Malaysia.
Received: 22 January 2022 Accepted: 22 May 2022
References
1. World Health Organization. 2019-nCoV outbreak is an emergency of
international concern. 2020.
2. World Health Organization. Naming the coronavirus disease (COVID-19)
and the virus that causes it. 2020. https://​www.​who.​int/​emerg​encies/​
disea​ses/​novel-​coron​avirus-​2019/​techn​ical-​guida​nce/​naming-​the-​coron​
avirus-​disea​se-​(covid-​2019)-​and-​the-​virus-​that-​causes-​it.
Sengupta and Dutta Middle East Fertility Society Journal (2022) 27:14 Page 6 of 6

3. Jordan RE, Adab P, Cheng K (2020) Covid-19: risk factors for severe disease 27. Ullian ME, Gelasco AK, Fitzgibbon WR, Beck CN, Morinelli TA (2005)
and death. Brit Med J 368:m1198 N-acetylcysteine decreases angiotensin ii receptor binding in vascular
4. Lu R, Zhao X, Li J, Niu P, Yang B, Wu H et al (2020) Genomic characterisa- smooth muscle cells. J Am Soc Nephrol 16:2346–2353
tion and epidemiology of 2019 novel coronavirus: implications for virus 28. Boesgaard S, Aldershvile J, Poulsen HE, Christensen S, Dige-Petersen H,
origins and receptor binding. Lancet 395(10224):565–574 Giese J (1993) N-acetylcysteine inhibits angiotensin converting enzyme
5. Wang Z, Xu X (2020) scRNA-seq profiling of human testes reveals the in vivo. J Pharmacol Exp Ther 265:1239–1244
presence of the ACE2 receptor, a target for SARS-CoV-2 infection in 29. McCarty MF, DiNicolantonio JJ (2020) Nutraceuticals have potential for
spermatogonia, Leydig and Sertoli cells. Cells 9(4):920 boosting the type 1 interferon response to RNA viruses including influ-
6. Wan Y, Shang J, Graham R, Baric RS, Li F (2020) Receptor recognition by enza and coronavirus. Prog Cardiovas Dis 63(3):383
the novel coronavirus from Wuhan: an analysis based on decade-long 30. Sengupta P, Dutta S, Slama P, Roychoudhury S (2022) COVID-19, oxidative
structural studies of SARS coronavirus. J Virol 94(7):e00127–e00120 stress, and male reproductive dysfunctions: vitamin C as a potential
7. Shastri A, Wheat J, Agrawal S, Chaterjee N, Pradhan K, Goldfinger M et al remedy? Physiol Res 71(1):47–54
(2020) Delayed clearance of SARS-CoV2 in male compared to female 31. Mata M, Morcillo E, Gimeno C, Cortijo J (2011) N-acetyl-L-cysteine (NAC)
patients: high ACE2 expression in testes suggests possible existence of inhibit mucin synthesis and pro-inflammatory mediators in alveolar type
gender-specific viral reservoirs. medRxiv. https://​doi.​org/​10.​1101/​2020.​04.​ II epithelial cells infected with influenza virus A and B and with respiratory
16.​20060​566 syncytial virus (RSV). Biochem Pharmacol 82(5):548–555
8. Dutta S, Sengupta P (2021) SARS-CoV-2 and male infertility: possible 32. Polonikov A (2020) Endogenous deficiency of glutathione as the most
multifaceted pathology. Reprod Sci 28(1):23–26 likely cause of serious manifestations and death in COVID-19 patients.
9. Sengupta P, Dutta S (2020) Does SARS-CoV-2 infection cause sperm ACS Infect Dis 6(7):1558–1562
DNA fragmentation? Possible link with oxidative stress. Eur J Contracept 33. Lai KY, Ng WY, Osburga Chan PK, Wong KF, Cheng F (2010) High-dose
Reprod Health Care 25(5):405–406 N-acetylcysteine therapy for novel H1N1 influenza pneumonia. Ann Int
10. Sengupta P, Dutta S (2021) COVID-19 and hypogonadism: secondary Med 152(10):687–688
immune responses rule-over endocrine mechanisms. Hum Fertil. https://​ 34. De Flora S, Grassi C, Carati L (1997) Attenuation of influenza-like symp-
doi.​org/​10.​1080/​14647​273.​2020.​18679​02 tomatology and improvement of cell-mediated immunity with long-term
11. Dutta S, Sengupta P (2020) SARS-CoV-2 infection, oxidative stress and N-acetylcysteine treatment. Eur Res J 10(7):1535–1541
male reproductive hormones: can testicular-adrenal crosstalk be ruled- 35. Garigliany MMO, Desmecht DJ (2011) N-acetylcysteine lacks universal
out? J Basic Clin Physiol Pharmacol 31(6):205 inhibitory activity against influenza A viruses. J Neg Results Biomed
12. Wambier CG, Goren A (2020) SARS-COV-2 infection is likely to be andro- 10(1):5
gen mediated. J Am Acad Dermatol 83:308–309 36. Fajgenbaum DC, Khor JS, Gorzewski A, Tamakloe M-A, Powers V, Kakkis JJ
13. de Kloet AD, Krause EG, Woods SC (2010) The renin angiotensin system et al (2020) Treatments administered to the first 9152 reported cases of
and the metabolic syndrome. Physiol Behav 100:525–534 COVID-19: a systematic review. Infect Dis Ther 2020(1):435–449
14. Wakahara S, Konoshita T, Mizuno S, Motomura M, Aoyama C, Makino Y, 37. Wright JH, Caudill R (2020) Remote treatment delivery in response to the
Kato N, Koni I, Miyamori I (2007) Synergistic expression of angiotensin- COVID-19 pandemic. Psychother Psychosom 89(3):1
converting enzyme (ace) and ace2 in human renal tissue and confound- 38. Memorial Sloan Kettering Cancer Center. A study of N-acetylcysteine in
ing effects of hypertension on the ace to ace2 ratio. Endocrinology patients with COVID-19 infection. 2020. Available from: https://​clini​caltr​
148:2453–2457 ials.​gov/​ct2/​show/​NCT04​374461.
15. Malhotra A, Kang BP, Cheung S, Opawumi D, Meggs LG (2001) Angioten-
sin II promotes glucose-induced activation of cardiac protein kinase C
isozymes and phosphorylation of troponin I. Diabetes 50:1918–1926 Publisher’s Note
16. Diaz JH (2020) Hypothesis: angiotensin-converting enzyme inhibitors and Springer Nature remains neutral with regard to jurisdictional claims in pub-
angiotensin receptor blockers may increase the risk of severe COVID-19. J lished maps and institutional affiliations.
Travel Med 27(3):taaa041
17. Kumar S, Maurya VK, Prasad AK, Bhatt MLB, Saxena SK (2020) Structural,
glycosylation and antigenic variation between 2019 novel coronavirus
(2019-nCoV) and SARS coronavirus (SARS-CoV). Virusdisease 31:13-21
18. Hoffmann M, Kleine-Weber H, Pöhlmann S (2020) A multibasic cleavage
site in the spike protein of SARS-CoV-2 is essential for infection of human
lung cells. Mol Cell 78(4):779–784
19. Thimon V, Belghazi M, Dacheux JL, Gatti JL (2006) Analysis of furin ecto-
domain shedding in epididymal fluid of mammals: demonstration that
shedding of furin occurs in vivo. Reproduction 132:899–908
20. Aldini G, Altomare A, Baron G, Vistoli G, Carini M, Borsani L, Sergio F (2018)
N-acetylcysteine as an antioxidant and disulphide breaking agent: the
reasons why. Free Rad Res 52:751–762
21. Jorge-Aarón R-M, Rosa-Ester MP (2020) N-acetylcysteine as a potential
treatment for novel coronavirus disease 2019. Fut Med 15(11):959–962
22. Schoeman D, Fielding BC (2019) Coronavirus envelope protein: current
knowledge. Virol J 16:1–22
23. Shittu SA, Shittu ST, Akindele OO, Kunle-Alabi OT, Raji Y (2019) Protec-
tive action of n-acetylcysteine on sperm quality in cyclophosphamide-
induced testicular toxicity in male wistar rats. JBRA Assist Reprod 23:83
24. Jannatifar R, Parivar K, Roodbari NH, Nasr-Esfahani MH (2019) Effects of
n-acetyl-cysteine supplementation on sperm quality, chromatin integrity
and level of oxidative stress in infertile men. Reprod Biol Endocrinol
17:1–9
25. Codrington AM, Hales BF, Robaire B (2004) Spermiogenic germ cell
phase—specific DNA damage following cyclophosphamide exposure. J
Androl 25:354–362
26. Ankem MK, Mayer E, Ward WS, Cummings KB, Barone JG (2002) Novel
assay for determining DNA organization in human spermatozoa: implica-
tions for male factor infertility. Urology 59:575–578